CN101002765A - Compressed formed preparation - Google Patents
Compressed formed preparation Download PDFInfo
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- CN101002765A CN101002765A CNA2006101564628A CN200610156462A CN101002765A CN 101002765 A CN101002765 A CN 101002765A CN A2006101564628 A CNA2006101564628 A CN A2006101564628A CN 200610156462 A CN200610156462 A CN 200610156462A CN 101002765 A CN101002765 A CN 101002765A
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- crystalline cellulose
- compressed
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid, pantothenic acid
- A61K31/198—Alpha-aminoacids, e.g. alanine, edetic acids [EDTA]
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/365—Lactones
- A61K31/375—Ascorbic acid, i.e. vitamin C; Salts thereof
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
- A61K47/38—Cellulose; Derivatives thereof
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
Abstract
The object of the invention is to provide a small troche which contains high content L-cysteine and ascorbic acid as medicinal composition as well as has excellent prepare-ability. The object is to provides a compression molding preparation which is characterized in containing 20 to 40 wt. % L-cysteine or the salt of L-Cysteine whose L-Cysteine calculated content is 20 to 40 wt. %, 30 to 70 wt. % ascorbic acid or the salt of ascorbic acid whose ascorbic acid calculated content is 30 to 70 wt. %, multi-crystalline cellulose whose content is totaled 7.5 to 25 wt. %, and 1 to 20 wt. % high-swelling property macromolecule.
Description
Technical field
The present invention relates to a kind of compressed-shaping formulation, more specifically, relate to a kind of compressed-shaping formulation that contains high-load L-cysteine and ascorbic acid as active ingredient.
Background technology
The preparation that allotment L-cysteine and ascorbic acid form, be in the past be used for pigment precipitation disease, general lassitudees such as senile plaque, freckle, tanned, macule, be still drank after a night, comedo, eczema, urticaria, macule, drug eruption, dental bed are hemorrhage, when the prevention of epistaxis, physical fatigue, during after being ill flag of pregnancy, age of sucking, disease, senile vitamin C supply etc.
And, for example for senile plaque, freckle, pigment precipitation disease, general lassitude such as tanned, be still drank after a night, comedo, eczema, urticaria, macule, drug eruption, the dose that is to use L-cysteine every day is that 240 milligrams, the dose of ascorbic acid are that the dose of 300 milligrams and calcium pantothenate is 24 milligrams a sugar-coated ingot.And when the hemorrhage prevention of, epistaxis hemorrhage, physical fatigue, in the pregnancy, age of sucking, disease during after being ill flag for pigment precipitation diseases such as senile plaque, freckle, tanned, macule, dental bed, senile vitamin C supply, being to use every day L-cysteine dose is that the dose of 30～160 milligrams and ascorbic acid is the various preparations that 300～1200 milligrams allotment L-cysteine and ascorbic acid form.
But because the dose of L-cysteine and ascorbic acid every day is all big, particularly the flowability of L-cysteine is poor, compression forming is also poor, when preparation changes into to lozenge, must add a large amount of excipient.And, use excipient in a large number, if when L-cysteine and content of ascorbic acid become big, can produce that every ingot weight becomes many and the problem that becomes large-scale lozenge.
To this, though also can consider the weight of per 1 ingot is reduced, lozenge is diminished and take, the number of lozenges increase of taking for 1 time this moment can become for patients and is difficult to take.In addition, because the flowability of ascorbic acid and compression forming are preferable, though can increase content of ascorbic acid in 1 ingot, as mentioned above, because the flowability of L-cysteine is poor, it is difficult increasing content.
As mentioned above, the preparation that allotment L-cysteine and ascorbic acid form, mostly be used for the treatment of pigment precipitation diseases such as senile plaque, freckle, tanned, macule, but the change of skin needs the time, also different because of each one, its effect will display must take about 3 months continuously, in so long-time, take the lozenge of large-scale lozenge or most amounts, can not feel just for patients that convenience is poor, can cause compliance property (compliance) to reduce, can become one of reason that effect can't give full play to yet.
In fact, the formulation examples 2.2 of patent documentation 1, formulation examples 2.3, and formulation examples 2.4 shown in the time contain the lozenge of L-cysteine and ascorbic acid, content of ascorbic acid is low to moderate about 18 weight %, the content of L-cysteine is low to moderate 9～15 weight %.In addition, patent documentation 2, patent documentation 3, patent documentation 4, patent documentation 5, and patent documentation 6, the content that discloses the ascorbic acid of the plain ingot of per 1 ingot and L-cysteine adds up to 60 weight % greater than plain ingot, although but this type of plain ingot content of ascorbic acid reaches 45～56%, the L-cysteine content of any all is low to moderate 8～19 weight % in them.
And in patent documentation 7, though the content of clear record L-cysteine is 22 weight %, its content of ascorbic acid is few to 28 weight %; The content of L-cysteine is more than the 20 weight % in plain ingot, and contains the good plain ingot of ascorbic acid, manufacturing of 30 weight %, does not up to the present provide as yet.
And, the lozenge that contains L-cysteine and ascorbic acid, promptly allow to carry out a spot of ingot of beating, but if when carrying out mass production, because the formulation additives of the excipient of being allocated etc., its mobile difference and can't play ingot or generation is cohered or the deviation of beating ingot obstacle or component content of gland (capping) becomes big, deviation of weight and becomes greatly, and can't make efficiently.In addition, become lozenge,, when plain ingot applies film coated or sugar-coat,, in preservation, also have and produce variable color or disruptive situation even component content does not reduce in order to reach the purpose that prevents the cysteine taste even if can play ingot.
[patent documentation 1] spy opens 2004-217655
[patent documentation 2] spy opens 2002-179559
[patent documentation 3] spy opens 2003-128543
[patent documentation 4] spy opens 2003-155232
[patent documentation 5] spy opens 2004-26786
[patent documentation 6] spy opens 2004-149426
[patent documentation 7] spy opens 2004-107273
Summary of the invention
[inventing problem to be solved]
Therefore, the purpose of this invention is to provide a kind of small-sized and high-quality lozenge, it contains high-load L-cysteine and ascorbic acid, the 20 weight % that respectively do for oneself are above and more than the 30 weight %, in order to the to greatest extent therapeutic effect of performance to pigment precipitation diseases such as senile plaque, freckle, tanned, macules.
[means of dealing with problems]
The present invention is in order to solve above-mentioned problem, the wholwe-hearted repeatedly result who discusses, discovery is by earlier in the combination carrier that crystalline cellulose and high swelling macromolecule form more than 2 kinds, allotment L-cysteine or its salt, with ascorbic acid or its salt, again with its compression forming, although can access a kind of L-cysteine and content of ascorbic acid height, little, the no component content deviation of the deviation of weight of lozenge or beat the ingot obstacle and can the good small-sized lozenge of mass-produced taking, and finished the present invention.
That is the purpose of this invention is to provide a kind of compressed-shaping formulation, it is characterized in that containing the ascorbic acid of the L-cysteine of 20～40 weight % or L-cysteine salt that L-cysteine conversion content is 20～40 weight %, 30～70 weight % or Ascorbate that ascorbic acid conversion content is 30～70 weight %, add up to the multiple crystalline cellulose of 7.5～25 weight % and the high swelling macromolecule of 1～20 weight %.
[effect of invention]
The present invention contains the compressed-shaping formulation as active ingredient such as L-cysteine and ascorbic acid, by allocating multiple crystalline cellulose and high swelling macromolecule, in L-cysteine that contains high concentration and ascorbic acid, can provide manufacturing good small-sized compressed-shaping formulation.
Therefore, the effect that L-cysteine and ascorbic acid etc. can be had, being effective as medicament uses, can provide a kind of to pigment precipitation disease, general lassitudees such as senile plaque, freckle, tanned, macules, be still drank after a night, comedo, eczema, urticaria, macule, drug eruption, dental bed are hemorrhage, when the hemorrhage prevention of epistaxis, physical fatigue, in the pregnancy, age of sucking, disease during after being ill flag, senile vitamin C supply etc., the compressed-shaping formulation that effect manifests really and takes easily.
The specific embodiment
Compressed-shaping formulation of the present invention (hereinafter referred to as " preparation of the present invention "), be by in containing multiple crystalline cellulose and the high molecular carrier of high swelling, allocate high-load L-cysteine or its salt earlier, reach ascorbic acid or its salt, again its compression forming is modulated.
In preparation of the present invention, the L-cysteine or its salt (hereinafter referred to as " L-cysteine class ") that are used as active ingredient, except L-cysteine itself, though can use the acid-addition salts etc. of the L-cysteine of L-cysteine hydrochloric acid etc., the preferred L-cysteine that uses.The dose of described L-cysteine class, when being scaled the L-cysteine, the adult is 10～1000 milligrams scope every day usually, preferred 30～480 milligrams, more preferably 160～240 milligrams.Described L-cysteine class is to take 1 time or be divided into 2～4 times in 1 day, preferably is divided into 2～3 times and takes.
L-cysteine class in the preparation of the present invention contain ratio, when being converted into the L-cysteine, preferred 20～40 weight %, more preferably 25～35 weight %, preferred especially 27.5～32.5 weight %.
On the other hand, in preparation of the present invention, the ascorbic acid or its salt (hereinafter referred to as " ascorbic acid class ") that are used as active ingredient, except ascorbic acid itself, can use the Ascorbate of calcium ascorbate, sodium ascorbate etc. or use and directly to play ingot with ascorbic acid, directly play ingot with calcium ascorbate and direct ingot any in sodium ascorbate of beating.In addition, above-mentioned ascorbic acid apoplexy due to endogenous wind preferably uses directly plays ingot with ascorbic acid, directly play ingot with calcium ascorbate, directly beat the ingot sodium ascorbate, and they can be available from BASF-TAKEDA VITAMIN (thigh).In the present invention, the dose of described ascorbic acid class, when being scaled ascorbic acid, the adult is 50～2000 milligrams scope every day usually, preferred 50～500 milligrams, preferred especially 200～400 milligrams.Described ascorbic acid class be with L-cysteine class similarly, 1 day 1 time or be divided into 2～4 times, preferably be divided into 2～3 times and take.
Ascorbic acid class in preparation of the present invention contain ratio, when being converted into ascorbic acid, preferred 30～70 weight %, more preferably 32.5～60 weight %, preferred especially 35～40 weight %.
Preparation of the present invention also can be allocated other pharmacological component except above-mentioned L-cysteine class and ascorbic acid class.Preferably, the example that can enumerate has pantothenic acid, calcium pantothenate, sodium pantothenate, pantothenic acid such as pantothenic acid alcohol, succinic acid d-alpha-tocopherol, succinic acid dl-alpha-tocopherol, succinic acid dl-alpha-tocopherol calcium, acetic acid d-alpha-tocopherol, acetic acid dl-alpha-tocopherol, the d-alpha-tocopherol, vitamin Es such as dl-alpha-tocopherol, hydrochloric tiamide (thiamine hydrochloride), nitric acid thiophene amine, the two thiophene amine of nitric acid, thiophene amine disulfide (thiaminedisulfide), thiophene amine diacetyl sulfuric ester, the bright hydrochloric acid of Fu Ersi amine (fursultiamine hydrochloride), salt acidic group generation first life (dicethiamine hydrochloride), Otto thiophene amine (octotiamine), but plug thiophene amine (cycotiamine), cloth thiophene amine (bisibutiamine) relaxes, two benzoyl thiophene amine (bisbentiamine), benzene phosphorus thiophene amine vitamin Bs such as (benfotiamne)
1, vitamin B such as riboflavin (riboflavin), Riboflavin butyrate, Riboflavin Sodium Phosphate
2, pyridoxine hydrochloride (pyridoxine hydrochloride), pyridoxal 5-phosphate vitamin Bs such as (pyridoxalphosphate)
6, cobalamin (cyanocobalamin), hydrochloric acid hydroxyl cobalt amine (hydrocobalaminhydrochloride), acetic acid hydroxyl cobalt amine (hydrocobalamin acetate), mecobalamin vitamin Bs such as (mecobalamin)
12, niacin, Semen Coicis, orotic acid, biotin, γ-Hi-Z, glucuronolactone, glucuronamide, coenzyme (ubidecarenon) etc. such as niacin, nicotianamine.More preferably pantothenic acid such as pantothenic acid, calcium pantothenate, sodium pantothenate, pantothenic acid alcohol wherein, its dose are 5～30 milligrams of adult preferred every days usually.
On the other hand, preparation of the present invention can use multiple crystalline cellulose as carrier.The example that described multiple crystalline cellulose can be enumerated have total body density (bulk density) more than 0.3 gram/cubic centimetre crystalline cellulose and total body density less than the combination of the crystalline cellulose of 0.3 gram/cubic centimetre.
Wherein, the crystalline cellulose of total body density more than 0.3 gram/cubic centimetre preferably uses the crystalline cellulose of total body density in 0.6 gram/cubic centimetre scope, and its object lesson has CEOLUS PH-301 (total body density 0.41 gram/cubic centimetre; The production of ASAHI KASEI CHEMICALS company), CEOLUSPH-301D (total body density 0.41 gram/cubic centimetre; The same), CEOLUS PH-301Z (total body density 0.41 gram/cubic centimetre; The same), CEOLUS PH-302 (total body density 0.43 gram/cubic centimetre; The same), CEOLUS PH-200 (total body density 0.33 gram/cubic centimetre; The same), CEOLUS PH-102 (total body density 0.30 gram/cubic centimetre; The same), VIVAPUR-103 (total body density 0.32 gram/cubic centimetre; J.RETTENMAIER﹠amp; The production of SOEHNE company), VIVAPUA-301 (total body density 0.38 gram/cubic centimetre; The same), VIVAPUA-102 (total body density 0.31 gram/cubic centimetre; The same), VIVAPUA-112 (total body density 0.35 gram/cubic centimetre; The same), VIVAPUA-12 (total body density 0.33 gram/cubic centimetre; The same), VIVAPUA-200 (total body density 0.34 gram/cubic centimetre; The same) etc.They can by a kind or mix 2 kinds with on use.Among them, preferred mean diameter is the crystalline cellulose more than 90 microns, the example that can enumerate has CEOLUS PH-302, CEOLUS PH-200, CEOLUS PH-102, VIVAPUA-112, VIVAPUA-102, VIVAPUA-12, VIVAPUA-200 etc., more preferably mean diameter is the crystalline cellulose more than 120 microns, and the example that can enumerate has VIIVAPUA-12, VIVAPUA-200, CEOLUSPH-200 etc.
On the other hand, total body density preferably uses the above crystalline cellulose of total body density to 0.10 gram/cubic centimetre less than the crystalline cellulose of 0.3 gram/cubic centimetre, and its object lesson has CEOLUS KG-802 (total body density 0.21 gram/cubic centimetre; The production of ASAHI KASEI CHEMICALS company), CEOLUSPH-20JP (total body density 0.23 gram/cubic centimetre; The same), CEOLUS PH-101 (total body density 0.29 gram/cubic centimetre; The same), CEOLUS PH-101D (total body density 0.29 gram/cubic centimetre; The same), VIVAPUA-105 (total body density 0.23 gram/cubic centimetre; J.RETTENMAIER﹠amp; The production of SOEHNE company), VIVAPUA-101 (total body density 0.29 gram/cubic centimetre; The same) etc.They can by a kind or mix 2 kinds with on use.Among them, preferred mean diameter is the crystalline cellulose more than 50 microns, the example that can enumerate has CEOLUS KG-802, CEOLUS PH-101, CEOLUSPH-101D, VIVAPUA-101 etc., and more preferably, the example that can enumerate has the CEOLUS KG-802 of total body density minimum.Gross weight with respect to preparation of the present invention, the addition of above-mentioned crystalline cellulose is difference to some extent according to the gross weight of the content of L-cysteine and ascorbic acid etc. or lozenge, total body density more than 0.3 gram/cubic centimetre crystalline cellulose and total body density less than the total amount of the crystalline cellulose of 0.3 gram/cubic centimetre, preferred 7.5～25 weight %, the more preferably scope of 15～20 weight %.Situation separately is the gross weight with respect to preparation of the present invention, preferred 5～23 weight % of the addition of the crystalline cellulose of total body density more than 0.3 gram/cubic centimetre, the more preferably scope of 10～15 weight %.Total body density is less than preferred 1～20 weight % of the addition of the crystalline cellulose of 0.3 gram/cubic centimetre, the more preferably scope of 2.5～10 weight %.
In the present invention, crystalline cellulose and the total body density of total body density more than 0.3 gram/cubic centimetre preferably is used in combination with 8: 1～1: 4 weight ratio less than the crystalline cellulose of 0.3 gram/cubic centimetre, and more preferably 4: 1～1: 1 weight ratio is used in combination.Especially preferably be used in combination with 2.5: 1～1.5: 1 weight ratio.Among the above-mentioned crystalline cellulose, total body density more than the 0.3 gram/cubic centimetre can be when keeping good mouldability, improve contain high concentration L-cysteine beat the flowability of ingot usefulness powder when playing ingot, total body density is less than the crystalline cellulose of 0.3 gram/cubic centimetre, can improve the compression forming when playing ingot significantly, help the raising of lozenge hardness.
And, the employed high swelling macromolecule of preparation of the present invention be water-fast and swelling big.The high molecular characteristics of this high swelling are reactive low, by allotment L-cysteine class and ascorbic acid etc., can keep flowability before playing ingot, and compression forming is good, can not produce variable color etc. after the molding.The high swelling macromolecule of this kind can enumerate object lesson crosslinked carboxylic cellulose formiate sodium (croscarmellosesodium), low degree of substitution hydroxy propyl cellulose or polyvinylpolypyrrolidone (crospovidone) are arranged, they can or mix more than 2 kinds and to use by a kind.Among them, preferably, the object lesson that can enumerate has low-substituted hydroxypropyl cellulose (L-HPC), and preferred especially mean diameter is 50 microns L-HPC (LH-11 and LH-B1), the especially special preferably L-HPC of fibrous powder body (LH-11).
With respect to the gross weight of preparation of the present invention, the high molecular addition of described high swelling is 1～20 weight %, the more preferably scope of 2.5～10 weight % with respect to gross weight preferably.
Preparation of the present invention is by at pharmacological components such as above-mentioned L-cysteine class and ascorbic acid classes, in crystalline cellulose and the high swelling macromolecule, add well-known pharmaceutical additive according to necessity, excipient for example, bonding agent, disintegrating agent, lubricant, tranquilizer, surfactant, cosolvent, Reducing agent, buffer agent, adsorbent, flowing agent, antistatic agent, the smears, plasticizer, anti-binder, opacifier, polishing material, antioxidant, sweetener, change the flavor agent, freshener, coloring agent, send out pastil, spice, aromatic etc., adjust compression forming powder body, carry out compression forming by common method and make.
The employed pharmaceutical additive of preparation of the present invention, with the allotment of L-cysteine class and ascorbic acid class etc. under, can not produce after the preferred compressed molding variable color water soluble polymer, light silicon anhydride (siliconeacid anhydrides), saccharide, sugar alcohol, starch, Pulvis Talci, and magnesium stearate in more than a kind or 2 kinds.
Can not produce the water soluble polymer of variable color after above-mentioned and allotment, compression formings such as L-cysteine class and ascorbic acid class, the example that can enumerate has HYDROXY PROPYL METHYLCELLULOSE, hydroxy propyl cellulose, Polyethylene Glycol etc.In addition, the example that can enumerate of starch has alphalise starch, part alphalise starch, corn starch, potato starch, wheaten starch, rice starch etc.; The example that saccharide, sugar alcohol can be enumerated has lactose, mannitol, xylitol, dextrin, Sorbitol etc.The addition of above-mentioned water soluble polymer starch, saccharide, sugar alcohol, because variant with the method for making of powder body according to the size of compressed-shaping formulation or compression forming, can't specific its amount, with respect to the compressed-shaping formulation gross weight, be roughly 0～40 weight %.
In addition, among above-mentioned pharmaceutical additive, light silicon anhydride can increase compression forming with the flowability of powder body, has the moistening that prevents compressed-shaping formulation or the effect of set simultaneously.Described light silicon anhydride preferred mean diameter is 2～10 microns, and more preferably using mean diameter is 2～4 microns light silicon anhydride.With respect to total formulation weight amount of the present invention, its addition preferably uses 0.1～3 weight %, more preferably uses 0.2～1 weight %.
And with respect to total formulation weight amount of the present invention, the addition of both or any of Pulvis Talci and magnesium stearate preferably adds 0.1～3 weight %, more preferably uses 0.5～1.5 weight %.
The powder body that compression forming is used can directly use and mix powder that mentioned component forms or its part or all pelletize is used.During with this powder body pelletize, can utilize normally used comminution granulation, for example use the solution contain water or organic solvent or dispersion liquid spray granulation, stirring-granulating method, fluidized granulation method, rotate wet granulations such as comminution granulation, rotational flow comminution granulation, use the dry pelletizing method etc. of the densification comminution granulation etc. of the granulous bonding agent of powder.
Preparation of the present invention is to use single-shot formula Ingot pressing machine, rotary Ingot pressing machine etc., makes by compression forming.The pressure of compression forming of this moment preferably is adjusted at more than 200 kilograms/square centimeter, more preferably more than 400～2000 kilograms/square centimeter.In addition, the weight of preparation of the present invention is not restricted, and normally about 50～about 400 milligrams, preferred about 100～about 200 milligrams.Preferred this weight is corresponding to 1 unit of taking of taking or its integer/one (for example making the component content that can take 1 ingot～3 ingots etc.) at every turn at every turn.In addition, the size of preparation of the present invention, when for example being shaped to circular lozenge, about 4～about 12 millimeters usually of its diameters, preferred about 6～about 10 millimeters.Also can pass through disc type rubbing method (pan coating), fluidized bed rubbing method, rotation rubbing method, dry type rubbing method or combination said method etc. as the resulting compressed-shaping formulation of above-mentioned method, make the painting preparation or the sugar-coated preparation of instant capacity.At this moment, also can be earlier with the film agent of water solublity or gastric solubility, to dissolve or be dispersed in water or the organic solvent, this type of film agent is perhaps directly sprayed in the coating of spraying, and the dry type coating is carried out in reheat or pressurization.And film agent also can add plasticizer, anti-binder, opacifier, extender, coloring agent and send out spice etc.
The preferred forms of compressed-shaping formulation of the present invention discussed above, be to use the L-cysteine that contains 27.5～32.5 weight %, the ascorbic acid of 35～40 weight %, and the total body density that allotment accounts for gross weight 15～20 weight % is more than 0.3 gram/cubic centimetre and its mean diameter is the crystalline cellulose more than 120 microns, its mean diameter is the crystalline cellulose more than 50 microns 2.5 the total body density of～10 weight % is less than 0.3 gram/cubic centimetre, 0.1 the high molecular low-substituted hydroxypropyl cellulose of the high swelling of the conduct of～5 weight %, the light silicon anhydride of 1～10 weight %, 0.1 the Pulvis Talci of～3 weight % and/or magnesium stearate and the compression forming powder body that obtains.Employed pressure is more than 400～2000 kilograms/square centimeter during compression forming, is about 100～about 200 milligrams, the about 6～about 10 millimeters mode of diameter with the weight of each preparation, compression forming and make compressed-shaping formulation.
[effect]
Make the employed ingot powder of beating of preparation of the present invention, although the content height of L-cysteine class and ascorbic acid class, but because contain 2 kinds of crystalline cellulose and high swelling macromolecules that total body density is different, flowability is still very good, is the compression forming excellent product.
Therefore, using this dozen ingot powder, by the prepared preparation of the present invention of high speed Ingot pressing machine, also can not produce dozen ingot obstacle even carry out mass production, is the small-sized lozenge that component content deviation or deviation of weight are little, taking is good.
[embodiment]
Below enumerate embodiment, be described more specifically the present invention, but the present invention is not subjected to any restriction of these embodiment.
Embodiment 1
The manufacturing (1) of plain ingot
960 gram L-cysteine, 1237.2 grams are directly played ingot restrain crystalline cellulose (VIVAPUA-12:J.RETTENMAIER﹠amp with ascorbic acid, 96 gram calcium pantothenates, 458.8; The production of SOEHNE company), 200 gram crystalline cellulose (CELOUS KG-802; The production of ASAHI KASEI CHEMICALS company), 200 gram low-substituted hydroxypropyl celluloses (LH-11: chemical industrial company of SHIN-ETSU HANTOTAI produces) and 16 gram light silicon anhydrides (production of ADOSORIDA-101:FREUND industry company) mixed 15 minutes, add 32 gram magnesium stearate again, mixed 1 minute, re-use rotary Ingot pressing machine with the resulting particulate compression forming that is used for compression forming, obtain the plain ingot (compressed-shaping formulation) of 8 millimeters of diameters, 4.3 millimeters of thickness, 200 milligrams of weight.
Embodiment 2
The manufacturing (2) of plain ingot
960 gram L-cysteine, 1237.2 grams are directly played ingot restrain crystalline cellulose (VIVAPUA-12:J.RETTENMAIER﹠amp with ascorbic acid, 147.6 gram calcium pantothenate type S, 336.4; The production of SOEHNE company), 196 gram crystalline cellulose (CELOUS KG-802; The production of ASAHI KASEI CHEMICALS company), 196 gram low-substituted hydroxypropyl celluloses (LH-11: chemical industrial company of SHIN-ETSU HANTOTAI produces) and 15.6 gram light silicon anhydrides (production of ADOSORIDA-101:FREUND industry company) mixed 15 minutes, add 31.2 gram magnesium stearate again, mixed 1 minute, re-use rotary Ingot pressing machine with the resulting particulate compression forming that is used for compression forming, obtain the plain ingot (compressed-shaping formulation) of 7 millimeters of diameters, 3.8 millimeters of thickness, 130 milligrams of weight.
Embodiment 3
The manufacturing of film coated ingot
960 gram L-cysteine, 1237.2 grams are directly played ingot restrain crystalline cellulose (VIVAPUA-12:J.RETTENMAIER﹠amp with ascorbic acid, 147.6 gram calcium pantothenate type S, 407.2; The production of SOEHNE company), 200 gram crystalline cellulose (CELOUS KG-802; The production of ASAHI KASEI CHEMICALS company), 200 gram low-substituted hydroxypropyl celluloses (LH-11: chemical industrial company of SHIN-ETSU HANTOTAI produces) and 16 gram light silicon anhydrides (production of ADOSORIDA-101:FREUND industry company) mixed 15 minutes, add 32 gram magnesium stearate again, mixed 1 minute, re-use rotary Ingot pressing machine with the resulting particulate compression forming that is used for compression forming, obtain the plain ingot (compressed-shaping formulation) of 8 millimeters of diameters, 4.3 millimeters of thickness, 200 milligrams of weight.
Then, should put into coating pan by the element ingot, and use the ethanol contain 5 weight % HYDROXY PROPYL METHYLCELLULOSE: the coating fluid of Purified Water=1: 1, gaining in weight with 1 ingot is that 10 milligrams mode is coated with, and obtains the film coated ingot.
Embodiment 4
The manufacturing of sugar-coated ingot
960 gram L-cysteine, 1237.2 grams are directly played ingot restrain crystalline cellulose (VIVAPUA-12:J.RETTENMAIER﹠amp with ascorbic acid, 96 gram calcium pantothenates, 388; The production of SOEHNE company), 196 gram crystalline cellulose (CELOUS KG-802; The production of ASAHI KASEI CHEMICALS company), 196 gram low-substituted hydroxypropyl celluloses (LH-11: chemical industrial company of SHIN-ETSU HANTOTAI produces) and 15.6 gram light silicon anhydrides (production of ADOSORIDA-101:FREUND industry company) mixed 15 minutes, add 31.2 gram magnesium stearate again, mixed 1 minute, re-use rotary Ingot pressing machine with the resulting particulate compression forming that is used for compression forming, obtain the plain ingot (compressed-shaping formulation) of 7 millimeters of diameters, 3.8 millimeters of thickness, 130 milligrams of weight.
Then, should put into coating pan by the element ingot, and use the ethanol contain 5 weight % HYDROXY PROPYL METHYLCELLULOSE: the coating fluid of Purified Water=1: 1, gaining in weight with 1 ingot is that 10 milligrams mode is coated with.
Then, utilize the aqueous solution contain 2 weight %, 2 weight % titanium oxides, 3 weight % calcium carbonate, 1 weight % gum arabic powder and 60 weight % castor sugars, gaining in weight with per 1 ingot is that 85 milligrams mode is coated with.Subsequently, utilize the aqueous solution of the castor sugar contain 60 weight %, gaining in weight with per 1 ingot is that 15 milligrams mode is coated with, and obtains sugar-coated ingot.
Comparative example 1
The manufacturing of more plain ingot (1)
Except 458.8 gram crystalline cellulose (VIVAPUA-12:J.RETTENMAIER﹠amp with embodiment 1; SOEHNE company produces) and 200 gram crystalline cellulose (CELOUSKG-802; ASAHI KASEI CHEMICALS company produces), change to 658.8 gram crystalline cellulose (CELOUS KG-802; ASAHI KASEI CHEMICALS company produces) in addition, carry out operation similarly to Example 1, make the plain ingot of comparison (relatively compressed-shaping formulation).
Comparative example 2
The manufacturing of more plain ingot (2)
Except 458.8 gram crystalline cellulose (VIVAPUA-12:J.RETTENMAIER﹠amp with embodiment 1; SOEHNE company produces) and 200 gram crystalline cellulose (CELOUSKG-802; ASAHI KASEI CHEMICALS company produces), change to 658.8 gram crystalline cellulose (VIVAPUA-12:J.RETTENMAIER﹠amp; SOEHNE company produces) in addition, carry out operation similarly to Example 1, make the plain ingot of comparison (relatively compressed-shaping formulation).
Comparative example 3
The manufacturing of more plain ingot (3)
Except 458.8 gram crystalline cellulose (VIVAPUA-12:J.RETTENMAIER﹠amp with embodiment 1; SOEHNE company produces) and 200 gram low-substituted hydroxypropyl celluloses (LH-11: chemical industrial company of SHIN-ETSU HANTOTAI produces), change to 658.8 gram crystalline cellulose (VIVAPUA-12:J.RETTENMAIER﹠amp; SOEHNE company produces) in addition, carry out operation similarly to Example 1, though make the plain ingot of comparison (relatively compressed-shaping formulation), produce gland (capping).
Test example 1
The deviation of weight test:
To the plain ingot of embodiment 1～4 and plain each 20 ingot of ingot of comparison of comparative example 1 and 2, the weight of measuring is separately investigated deviation of weight.The result is shown in the CV value (%) of table 1.Any one deviation of weight of plain ingot of preparation of the present invention is all little, and the deviation of weight of the plain ingot of comparative example 1 is big.
[table 1]
| Preparation | Deviation of weight CV value (%) |
| Embodiment 1 | 0.66 |
| Embodiment 2 | 0.75 |
| Embodiment 3 | 0.58 |
| Embodiment 4 | 0.69 |
| Comparative example 1 | 2.03 |
| Comparative example 2 | 0.62 |
Test example 2
Lozenge hardness:
To the plain ingot of embodiment 1～4 and plain each 10 ingot of ingot of comparison of comparative example 1 and 2, use lozenge durometer (TH-303MP type lozenge breaking strength measuring device; Fushan Mountain industry (thigh) system), measure hardness separately.The result is as shown in table 2.When the plain ingot of the comparison element ingot of comparative example 2 and onesize embodiment 1 and 3 compared, hardness was little a lot.
[table 2]
| Preparation | Lozenge hardness (N) |
| Embodiment 1 | 51.0 |
| Embodiment 2 | 41.3 |
| Embodiment 3 | 50.2 |
| Embodiment 4 | 42.1 |
| Comparative example 1 | 67.0 |
| Comparative example 2 | 34.6 |
Claims (7)
1, a kind of compressed-shaping formulation is characterized in that containing the ascorbic acid of the L-cysteine of 20～40 weight % or L-cysteine salt that L-cysteine conversion content is 20～40 weight %, 30～70 weight % or Ascorbate that ascorbic acid conversion content is 30～70 weight %, adds up to the multiple crystalline cellulose of 7.5～25 weight % and the high swelling macromolecule of 1～20 weight %.
2, compressed-shaping formulation as claimed in claim 1, a kind of in the wherein said multiple crystalline cellulose is the crystalline cellulose of total body density more than 0.3 gram/cubic centimetre, another kind is the crystalline cellulose of total body density less than 0.3 gram/cubic centimetre.
3, compressed-shaping formulation according to claim 1 and 2, wherein said total body density is 8: 1～1: 4 at the crystalline cellulose of 0.3 gram/cube more than the claim and total body density less than the ratio of the crystalline cellulose of 0.3 gram/cube claim.
4, compressed-shaping formulation according to claim 1, wherein said high swelling macromolecule is the macromolecule that is selected from low-substituted hydroxypropyl cellulose, crosslinked carboxylic cellulose formiate sodium or polyvinylpolypyrrolidone more than a kind or 2 kinds.
5, compressed-shaping formulation according to claim 1, wherein further contain be selected from more than a kind or 2 kinds water soluble polymer, light silicon anhydride, saccharide, sugar alcohol, starch, Pulvis Talci, and magnesium stearate in composition.
6, compressed-shaping formulation according to claim 1 wherein further uses the thin, water soluble membrane to come the coated formulation surface.
7, compressed-shaping formulation according to claim 1 wherein further uses sugar-coat to come the coated formulation surface.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2006007331 | 2006-01-16 | ||
| JP2006007331A JP5021210B2 (en) | 2006-01-16 | 2006-01-16 | Compression molding |
| JP2006-007331 | 2006-01-16 |
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| CN101002765A true CN101002765A (en) | 2007-07-25 |
| CN101002765B CN101002765B (en) | 2011-10-12 |
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| CN2006101564628A Active CN101002765B (en) | 2006-01-16 | 2006-12-31 | Compressed formed preparation |
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| JP (1) | JP5021210B2 (en) |
| KR (1) | KR101364561B1 (en) |
| CN (1) | CN101002765B (en) |
| HK (1) | HK1104234A1 (en) |
| TW (1) | TWI414287B (en) |
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| RU2527766C2 (en) | 2009-03-13 | 2014-09-10 | Тояма Кемикал Ко., Лтд. | Tablets and granulated powders containing 6-fluor-3-hydroxy-2-pyrazincarboxamide |
| JP5733930B2 (en) * | 2009-09-09 | 2015-06-10 | 武田薬品工業株式会社 | Solid preparation |
| RS56032B1 (en) * | 2013-01-15 | 2017-09-29 | Fujifilm Corp | Tablet containing 5-hydroxy-1h-imidazole-4-carboxamide |
| JP6327237B2 (en) * | 2014-12-05 | 2018-05-23 | 大正製薬株式会社 | Solid composition |
| JP7330716B2 (en) * | 2019-02-21 | 2023-08-22 | アサヒグループ食品株式会社 | Method for suppressing discoloration of composition containing amino acid or its salt and vitamin C, powder composition, granules, and tablet |
| JP6676816B1 (en) * | 2019-05-31 | 2020-04-08 | シオノギヘルスケア株式会社 | L-cysteine-containing vitamin C-rich compression molded preparation |
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| JP2001322927A (en) * | 2000-05-12 | 2001-11-20 | Shin Etsu Chem Co Ltd | Solid preparation including hydroxypropyl cellulose of low substitution degree and method for preparation of the same |
| JP2002179559A (en) * | 2000-10-06 | 2002-06-26 | Takeda Chem Ind Ltd | Thin-layer sugar-coated tablet and method for producing the same |
| JP2004026786A (en) * | 2002-05-10 | 2004-01-29 | Takeda Chem Ind Ltd | Vitamin preparation |
| CN1593411A (en) * | 2004-01-15 | 2005-03-16 | 范敏华 | Speckle removing pharmaceutical composition |
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| JP2007186470A (en) | 2007-07-26 |
| JP5021210B2 (en) | 2012-09-05 |
| KR101364561B1 (en) | 2014-02-18 |
| TWI414287B (en) | 2013-11-11 |
| CN101002765B (en) | 2011-10-12 |
| HK1104234A1 (en) | 2008-01-11 |
| KR20070076388A (en) | 2007-07-24 |
| TW200744572A (en) | 2007-12-16 |
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